BIOACTIVE MARINE MICROBIAL METABOLITES

生物活性海洋微生物代谢物

• 批准号: 2882202
• 负责人: Hao Chen
• 金额: $ 38.16万
• 依托单位: NOVASCREEN BIOSCIENCES CORPORATION
• 依托单位国家: 美国
• 财政年份: 1996
• 资助国家: 美国
• 起止时间: 1996-09-01 至 2000-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2882202
• 关键词: Candida; Enterococcus; Escherichia coli; Pseudomonas aeruginosa; Staphylococcus aureus; anaerobic bacteria; antibacterial agents; antiinflammatory agents; aquatic organism; biological products; chemical structure; drug discovery /isolation; drug resistance; drug screening /evaluation; guinea pigs; high performance liquid chromatography; laboratory mouse; mass spectrometry; microorganism; microorganism culture; nuclear magnetic resonance spectroscopy; pharmacology; receptor binding

This SBIR Phase II Grant Application has as its goal the discovery, development and commercialization of new, small molecule drugs which have their origin as natural products elaborated by marine microorganisms. Initial disease targets for drug development include: i) new antibiotics which are broadly effective against microbial pathogens and are effective in controlling pathogens resistant to currently utilized antibiotic drugs, and ii) new drugs able to modulate inflammatory process and suppress subsequent allergic responses. Marine microorganisms represent a vast, unexplored, and promising source material for the discovery of novel drugs. Work completed under Phase I of this Application was successful in establishing routine methods and manipulations to circumvent difficulties traditionally associated with drug discovery efforts employing marine microorganisms. These inherent difficulties include the isolation and growth of marine microorganisms, the stimulation of bioactive material production, and the removal or suppression of interfering media components during bioassay. Phase I work also resulted in the discovery of more than 20 highly active materials. Work proposed under Phase II represents the application and expansion of these routine methods and manipulations to a substantial bioactive materials discovery and development effort. The screening program will employ: i) a collection of taxonomically heterogeneous marine microbial isolates collected from widely diverse geographic regions and ecological niches, and ii) a battery of antibiotic assays, and targeted receptor binding based pharmacological assays. The active materials discovered in the screening component are advanced through assay guided fractination for compound isolation and prufication followed by a chemistry intensive effort focused on determining the structure of the active chemical moity. The most active drug materials will be advanced to pre-clinical development. PROPOSED COMMERCIAL APPLICATION Successful development and application of the proposed technology should revitalize the flow of novel, small molecule, natural product drug candidates into preclinical safety and efficacy testing programs. This Phase II Grant program is specially focused on developing new drugs to treat important disease categories comprising; I infectious diseases including those infections resulting from antibiotic resistant pathogens and ii) new treatment for inflammation and allergy.

SBIR II期赠款应用程序的目标是发现的目标， 新的小分子药物的开发和商业化，这些药物 将其起源于海军陆战队详细阐述的天然产品 微生物。 药物开发的最初疾病靶标包括： i）针对微生物的新抗生素有效 病原体，有效控制抗病的病原体 目前使用抗生素药物，ii）能够调节的新药 炎症过程并抑制随后的过敏反应。 海军陆战队 微生物代表着广阔，未开发且有前途的来源 发现新药的材料。 在阶段完成的工作 该应用程序的i成功地建立了常规方法和 操纵传统上与之相关的困难 使用海洋微生物的药物发现工作。 这些固有 困难包括海洋微生物的隔离和生长， 刺激生物活性材料产生以及去除或 在生物测定期间抑制干扰培养基组件。 第一阶段 工作还导致了20多个高度活跃的发现 材料。 根据第二阶段提出的工作代表申请， 将这些常规方法和操作扩展到实质性 生物活性材料发现和开发工作。 筛选 程序将采用：i）分类学异质的集合 从广泛的地理位置收集的海洋微生物分离株 区域和生态壁ches，ii）一电池抗生素测定， 和靶向受体结合的药理测定法。 活动 筛选组件中发现的材料通过 测定指导分裂的化合物隔离和衰退 其次是化学密集型努力，重点是确定 活性化学系列的结构。 最活跃的药物材料 将提高到临床前的发展。 拟议的商业应用 拟议技术的成功开发和应用应 振兴新颖，小分子，天然产品药物的流动 候选人参加临床前的安全性和有效性测试计划。 这 第二阶段赠款计划专门针对开发新药 治疗包括包括的重要疾病类别；我传染病 包括抗生素耐药病原体引起的感染 ii）炎症和过敏的新治疗方法。